Role of stromal-epithelial interactions in hormonal responses

Steroid sex hormones (17β-estradiol, testosterone, dihydrotestosterone, and progesterone) and aryl hydrocarbons such as the dioxins regulate epithelial proliferation and secretory protein production and differentiation in their respective target organs in male and female urogenital tracts and mammary glands. Recent evidence has demonstrated that stromal-epithelial interactions are critical for mediating the effects of these molecules on epithelial cells. Our results have indicated that estradiol, testosterone, progesterone, and dioxin regulate epithelial proliferation (stimulation or inhibition) via paracrine mechanisms requiring the appropriate receptor in the stroma. The androgen receptor (AR), estrogen receptor alpha (ERα), progesterone receptor (PR), or aryl hydrocarbon receptor (AhR) in the epithelium are neither necessary nor sufficient for the regulation of epithelial proliferation. Moreover, during prostatic development, signaling through the stromal AR is required to induce prostatic epithelial identity, ductal morphogenesis and glandular differentiation. Epithelial functional differentiation is regulated in the prostate, uterus, and vagina via AR (prostate) and ERα(uterus and vagina). In these organs both epithelial and stromal steroid receptors are required for steroidal regulation of certain aspects of epithelial differentiation such as epithelial secretory protein production in the uterus and epithelial cornification in the vagina and prostate (squamous metaplasia). The mechanistic basis of these stromal-epithelial interactions is poorly understood, but growth factors appear to be mediators of these cell-cell interactions.